Background: The hepatitis C pandemic has been systematically studied and characterized in North America and Europe, but this important public health problem has not received equivalent attention in ...other regions.
Aim: The objective of this systematic review was to characterize hepatitis C virus (HCV) epidemiology in selected countries of Asia, Australia and Egypt, i.e. in a geographical area inhabited by over 40% of the global population.
Methodology: Data references were identified through indexed journals and non‐indexed sources. In this work, 7770 articles were reviewed and 690 were selected based on their relevance.
Results: We estimated that 49.3–64.0 million adults in Asia, Australia and Egypt are anti‐HCV positive. China alone has more HCV infections than all of Europe or the Americas. While most countries had prevalence rates from 1 to 2% we documented several with relatively high prevalence rates, including Egypt (15%), Pakistan (4.7%) and Taiwan (4.4%). Nosocomial infection, blood transfusion (before screening) and injection drug use were identified as common risk factors in the region. Genotype 1 was common in Australia, China, Taiwan and other countries in North Asia, while genotype 6 was found in Vietnam and other Southeast Asian countries. In India and Pakistan genotype 3 was predominant, while genotype 4 was found in Middle Eastern countries such as Egypt, Saudi Arabia and Syria.
Conclusion: We recommend implementation of surveillance systems to guide effective public health policy that may lead to the eventual curtailment of the spread of this pandemic infection.
While tuberculosis (TB) remains a global disease, the WHO estimates that 62% of the incident TB cases in 2016 occurred in the WHO South-East Asia and Western Pacific regions. TB in the Pacific is ...composed predominantly of two genetic families of Mycobacterium tuberculosis (Mtb): Beijing and Manila. The Manila family is historically under-studied relative to the families that comprise the majority of TB in Europe and North America (e.g. lineage 4), and it remains unclear why this lineage has persisted in Filipino populations despite the predominance of more globally successful Mtb lineages in most of the world. The Beijing family is of particular interest as it is increasingly associated with drug resistance throughout the world. Both of these lineages are important to the State of Hawaii, where they comprise over two-thirds of TB cases. Here, we performed whole genome sequencing on 82 Beijing family, Manila family, and outgroup clinical Mtb isolates from Hawaii to identify lineage-specific SNPs (SNPs found in all isolates from their respective families, and exclusively in those families) in established virulence factor genes. Six non-silent lineage-specific virulence factor SNPs were found in the Beijing family, including mutations in alternative sigma factor sigG and polyketide synthases pks5 and pks7. The Manila family displayed more than eleven non-silent lineage-specific and characteristic virulence factor mutations, including in genes coding for MCE-family protein Mce1B, two mutations in fatty-acid-AMP ligase FadD26, and virulence-regulating transcriptional regulator VirS. This study further identified an ancient clade that shared some virulence factor mutations with the Manila family, and investigated the relationship of those and other "Manila-like" spoligotypes to the Manila family with this SNP dataset. This work identified a set of virulence genes that are worth pursuing to determine potential differences in transmission or virulence displayed by these two Mtb families.
Tuberculosis (TB) caused an estimated 1.4 million deaths and 10.4 million new cases globally in 2015. TB rates in the United States continue to steadily decline, yet rates in the State of Hawaii are ...perennially among the highest in the nation due to a continuous influx of immigrants from the Western Pacific and Asia. TB in Hawaii is composed of a unique distribution of genetic lineages, with the Beijing and Manila families of Mycobacterium tuberculosis (Mtb) comprising over two-thirds of TB cases. Standard fingerprinting methods (spoligotyping plus 24-loci Mycobacterial Interspersed Repetitive Units-Variable Number Tandem Repeats MIRU-VNTR fingerprinting) perform poorly when used to identify actual transmission clusters composed of isolates from these two families. Those typing methods typically group isolates from these families into large clusters of non-linked isolates with identical fingerprints. Next-generation whole-genome sequencing (WGS) provides a new tool for molecular epidemiology that can resolve clusters of isolates with identical spoligotyping and MIRU-VNTR fingerprints.
We performed WGS and SNP analysis and evaluated epidemiological data to investigate 19 apparent TB transmission clusters in Hawaii from 2003 to 2017 in order to assess WGS' ability to resolve putative Mtb clusters from the Beijing and Manila families. This project additionally investigated MIRU-VNTR allele prevalence to determine why standard Mtb fingerprinting fails to usefully distinguish actual transmission clusters from these two Mtb families.
WGS excluded transmission events in seven of these putative clusters, confirmed transmission in eight, and identified both transmission-linked and non-linked isolates in four. For epidemiologically identified clusters, while the sensitivity of MIRU-VNTR fingerprinting for identifying actual transmission clusters was found to be 100%, its specificity was only 28.6% relative to WGS. We identified that the Beijing and Manila families' significantly lower Shannon evenness of MIRU-VNTR allele distributions than lineage 4 was the cause of standard fingerprinting's poor performance when identifying transmission in Beijing and Manila family clusters.
This study demonstrated that WGS is necessary for epidemiological investigation of TB in Hawaii and the Pacific.
Individuals with both diabetes mellitus (DM) and TB infection are at higher risk of progressing to TB disease.
To determine DM prevalence in populations at high risk for latent TB infection (LTBI) ...and to identify the most accurate point-of-care (POC) method for DM screening.
Adults aged ≥25 years were recruited at health department clinics in Hawaii and Arizona, USA, and screened for LTBI and DM. Screening methods for DM included self-report, random blood glucose (RBG), and POC hemoglobin A1c (HbA1c). Using HbA1c ≥6.5% or self-reported history as the gold standard for DM, we compared test strategies to determine the most accurate method while keeping test costs low.
Of 472 participants, 13% had DM and half were unaware of their diagnosis. Limiting HbA1c testing to ages ≥30 years with a RBG level of 120-180 mg/dL helped identify most participants with DM (sensitivity 85%, specificity 99%) at an average test cost of US$2.56 per person compared to US$9.56 per person using HbA1c for all patients.
Self-report was insufficient to determine DM status because many participants were previously undiagnosed. Using a combination of POC RBG and HbA1c provided an inexpensive option to assess DM status in persons at high risk for LTBI.
Abstract
Background
Tuberculosis (TB) elimination within the United States will require scaling up TB preventive services. Many public health departments offer care for latent tuberculosis infection ...(LTBI), although gaps in the LTBI care cascade are not well quantified. An understanding of these gaps will be required to design targeted public health interventions.
Methods
We conducted a cohort study through the Tuberculosis Epidemiologic Studies Consortium (TBESC) within 15 local health department (LHD) TB clinics across the United States. Data were abstracted on individuals receiving LTBI care during 2016–2017 through chart review. Our primary objective was to quantify the LTBI care cascade, beginning with LTBI testing and extending through treatment completion.
Results
Among 23 885 participants tested by LHDs, 46% (11 009) were male with a median age of 31 (interquartile range IQR 20–46). A median of 35% of participants were US-born at each site (IQR 11–78). Overall, 16 689 (70%) received a tuberculin skin test (TST), 6993 (29%) received a Quantiferon (QFT), and 1934 (8%) received a T-SPOT.TB; 5% (1190) had more than one test. Among those tested, 2877 (12%) had at least one positive test result (3% among US-born, and 23% among non-US–born, P < .01). Of 2515 (11%) of the total participants diagnosed with LTBI, 1073 (42%) initiated therapy, of whom 817 (76%) completed treatment (32% of those with LTBI diagnosis).
Conclusions
Significant gaps were identified along the LTBI care cascade, with less than half of individuals diagnosed with LTBI initiating therapy. Further research is needed to better characterize the factors impeding LTBI diagnosis, treatment initiation, and treatment completion.
Significant gaps were identified at each step of the latent TB infection (LTBI) care cascade at health department clinics. Non-US–born individuals had higher prevalence of LTBI than US-born individuals. Overall, less than half of individuals diagnosed with LTBI initiated therapy.
T-SPOT.
(T-SPOT) is an interferon gamma release assay (IGRA) used to detect infection with
based on the number of spot-forming T cells; however, delays in sample processing have been shown to reduce ...the number of these spots that are detected following laboratory processing. Adding T-Cell Xtend (XT) into blood samples before processing reportedly extends the amount of time allowed between blood collection and processing up to 32 h. In this study, paired blood samples from 306 adolescents and adults at high risk for latent tuberculosis (TB) infection (LTBI) or progression to TB disease were divided into three groups: (i) early processing (∼4.5 h after collection) with and without XT, (ii) delayed processing (∼24 h after collection) with and without XT, and (iii) early processing without XT and delayed processing with XT. The participants' paired samples were processed at a local laboratory and agreement of qualitative and quantitative results was assessed. The addition of XT did not consistently increase or decrease the number of spots. In groups 1, 2, and 3, samples processed with XT had 13% (10/77), 28.0% (30/107), and 24.6% (30/122), respectively, more spots, while 33.8% (26/77), 26.2% (28/107), and 38.5% (47/122) had fewer spots than samples processed without XT. The findings suggest that XT does not reliably mitigate the loss of spot-forming T cells in samples with processing delay.
Ambitious population-based screening programmes for latent and active tuberculosis (TB) were implemented in the Republic of the Marshall Islands in 2017 and 2018.
We used a transmission dynamic model ...of TB informed by local data to capture the Marshall Islands epidemic's historical dynamics. We then used the model to project the future epidemic trajectory following the active screening interventions, as well as considering a counterfactual scenario with no intervention. We also simulated future scenarios including periodic interventions similar to those previously implemented, to assess their ability to reach the End TB Strategy targets and TB pre-elimination in the Marshall Islands.
The screening activities conducted in 2017 and 2018 were estimated to have reduced TB incidence and mortality by around one-third in 2020, and are predicted to achieve the End TB Strategy milestone of 50% incidence reduction by 2025 compared with 2015. Screening interventions had a considerably greater impact when latent TB screening and treatment were included, compared with active case finding alone. Such combined programmes implemented at the national level could achieve TB pre-elimination around 2040 if repeated every 2 years.
Our model suggests that it would be possible to achieve TB pre-elimination by 2040 in the Marshall Islands through frequent repetition of the same interventions as those already implemented in the country. It also highlights the importance of including latent infection testing in active screening activities.
Background and Aim: Decisions on public health issues are dependent on reliable epidemiological data. A comprehensive review of the literature was used to gather country‐specific data on risk ...factors, prevalence, number of diagnosed individuals and genotype distribution of the hepatitis C virus (HCV) infection in selected European countries, Canada and Israel.
Methodology: Data references were identified through indexed journals and non‐indexed sources. In this work, 13 000 articles were reviewed and 860 were selected based on their relevance.
Results: Differences in prevalence were explained by local and regional variances in transmission routes or different public health measures. The lowest HCV prevalence (≤0.5%) estimates were from northern European countries and the highest (≥3%) were from Romania and rural areas in Greece, Italy and Russia. The main risk for HCV transmission in countries with well‐established HCV screening programmes and lower HCV prevalence was injection drug use, which was associated with younger age at the time of infection and a higher infection rate among males. In other regions, contaminated glass syringes and nosocomial infections continue to play an important role in new infections. Immigration from endemic countries was another factor impacting the total number of infections and the genotype distribution. Approximately 70% of cases in Israel, 37% in Germany and 33% in Switzerland were not born in the country. In summary, HCV epidemiology shows a high variability across Europe, Canada and Israel.
Conclusion: Despite the eradication of transmission by blood products, HCV infection continues to be one of the leading blood‐borne infections in the region.
T-SPOT.TB (T-SPOT) is an interferon gamma release assay (IGRA) used to detect infection with Mycobacterium tuberculosis based on the number of spot-forming T cells; however, delays in sample ...processing have been shown to reduce the number of these spots that are detected following laboratory processing. Adding T-Cell Xtend (XT) into blood samples before processing reportedly extends the amount of time allowed between blood collection and processing up to 32 h. In this study, paired blood samples from 306 adolescents and adults at high risk for latent tuberculosis (TB) infection (LTBI) or progression to TB disease were divided into three groups: (i) early processing (∼4.5 h after collection) with and without XT, (ii) delayed processing (∼24 h after collection) with and without XT, and (iii) early processing without XT and delayed processing with XT. The participants’ paired samples were processed at a local laboratory and agreement of qualitative and quantitative results was assessed. The addition of XT did not consistently increase or decrease the number of spots. In groups 1, 2, and 3, samples processed with XT had 13% (10/77), 28.0% (30/107), and 24.6% (30/122), respectively, more spots, while 33.8% (26/77), 26.2% (28/107), and 38.5% (47/122) had fewer spots than samples processed without XT. The findings suggest that XT does not reliably mitigate the loss of spot-forming T cells in samples with processing delay.
Latent tuberculosis infection (LTBI) screening and treatment interventions that are tailored to optimize acceptance among the non-U.S.-born population are essential for U.S. tuberculosis elimination. ...We investigated the impact of medical interpreter use on LTBI treatment acceptance and completion among non-U.S.-born persons in a multisite study.
The Tuberculosis Epidemiologic Studies Consortium was a prospective cohort study that enrolled participants at high risk for LTBI at ten U.S. sites with 18 affiliated clinics from 2012 to 2017. Non-U.S.-born participants with at least one positive tuberculosis infection test result were included in analyses. Characteristics associated with LTBI treatment offer, acceptance, and completion were evaluated using multivariable logistic regression with random intercepts to account for clustering by enrollment site. Our primary outcomes were whether use of an interpreter was associated with LTBI treatment acceptance and completion. We also evaluated whether interpreter usage was associated treatment offer and whether interpreter type was associated with treatment offer, acceptance, or completion.
Among 8,761 non-U.S.-born participants, those who used an interpreter during the initial interview had a significantly greater odds of accepting LTBI treatment than those who did not use an interpreter. There was no association between use of an interpreter and a clinician's decision to offer treatment or treatment completion once accepted. Characteristics associated with lower odds of treatment being offered included experiencing homelessness and identifying as Pacific Islander persons. Lower treatment acceptance was observed in Black and Latino persons and lower treatment completion by participants experiencing homelessness. Successful treatment completion was associated with use of shorter rifamycin-based regimens. Interpreter type was not associated with LTBI treatment offer, acceptance, or completion.
We found greater LTBI treatment acceptance was associated with interpreter use among non-U.S.-born individuals.